I

15-20 divisions d. Nucleolar fragmentation, SIRp relocalization, sterility, death

Figure 3 rDNA circle model of yeast aging. (a) Young mother cells initially produced contain no ERCs. (b) At some frequency, the initiating event of the aging process is the generation of an ERC by intrachromosomal homologous recombination between rDNA units on chromosome 12. (c) Most daughter cells do not inherit an ERC, and the aging pheno-type is therefore not transmitted. The ERCs, which contain an origin of replication within the rDNA repeat, replicate during S phase and are maintained within the mother cell through asymmetrical segregation. (d) ERCs accumulate exponentially in mother cells resulting in nucleolar enlargement, nucleolar fragmentation, and cessation of cell division. In very old mother cells with high levels of ERCs, the asymmetrical segregation of ERCs may break down. This results in the accelerated senescence of some daughter cells of old mother cells that has been observed. (Adapted from Ref. 102.)

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